Heredity, Gene Regulation, and Development

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Heredity, Gene Regulation, and Development
Mutation A. Overview
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Mutation A. Overview 1) A mutation is a change
in the genome of a cell.
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Mutation A. Overview 1) A mutation is a change
in the genome of a cell. 2) Somatic
Mutations - can occur during DNA replication
prior to mitosis - can occur during DNA
repair - can be caused by exposure to a
mutagen - if uncorrected, can be passed to
daughter cells. - typically not the source of
heritable mutations
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Mutation A. Overview 1) A mutation is a change
in the genome of a cell. 2) Somatic
Mutations - can occur during DNA replication
prior to mitosis - can occur during DNA
repair - can be caused by exposure to a
mutagen - if uncorrected, can be passed to
daughter cells. - typically not the source of
heritable mutations 3) Germ-line Mutations -
occur in germ-line cells (tissues that produce
gametes or spores) - occur so early in
development, before germ-line cells have
differentiated, that they affect germ-line
cells. - occurs in DNA replication or meiosis,
producing mutant gametes/spores
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• VI. Mutation
• Overview
• 3) These changes in a genome can occur at four
  scales of genetic organization
• - Change in the number of sets of chromosomes
  ( change in ploidy)
• - Change in the number of chromosomes in a set
  (aneuploidy)
• - Change in the number and arrangement of
  genes on a chromosome
• (gene duplications, deletions, inversions,
  translocations)
• - Change in the nitrogenous base sequence
  within a gene
• (point mutations)

Typically, the larger the change, the more
dramatic (and negative) the result
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• VI. Mutation
• Overview
• Changes in Ploidy
• - These are the most dramatic changes, adding a
  whole SET of chromosomes

Triploidy occurs in 2-3 of all human
pregnancies, but almost always results in
spontaneous abortion of the embryo. Some
triploid babies are born alive, but die shortly
after. Syndactyly (fused fingers), cardiac,
digestive tract, and genital abnormalities occur.
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• VI. Mutation
• Overview
• Changes in Ploidy
• - These are the most dramatic changes, adding a
  whole SET of chromosomes
• Mechanism 1 Complete failure of Meiosis
• - if meiosis fails, reduction does not occur and
  a diploid gamete is produced. This can occur
  because of failure of homologs OR sister
  chromatids to separate in Meiosis I or II,
  respectively.

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• VI. Mutation
• Overview
• Changes in Ploidy
• - These are the most dramatic changes, adding a
  whole SET of chromosomes
• Mechanism 1 Complete failure of Meiosis
• - if meiosis fails, reduction does not occur and
  a diploid gamete is produced. This can occur
  because of failure of homologs OR sister
  chromatids to separate in Meiosis I or II,
  respectively.

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• VI. Mutation
• Overview
• Changes in Ploidy
• - These are the most dramatic changes, adding a
  whole SET of chromosomes
• Mechanism 1 Complete failure of Meiosis
• - if meiosis fails, reduction does not occur and
  a diploid gamete is produced. This can occur
  because of failure of homologs OR sister
  chromatids to separate in Meiosis I or II,
  respectively.
• - this results in a single diploid gamete, which
  will probably fertilize a normal haploid gamete,
  resulting in a triploid offspring.
• negative consequences of Triploidy
• 1) quantitative changes in protein production
  and developmental regulation.
• 2) cant reproduce sexually cant produce
  gametes if you are 3n.

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1) quantitative changes in protein production
and regulation. 2) cant reproduce sexually
cant produce gametes if you are 3n. 3)
BUT.
some organisms can survive, and reproduce
parthenogenetically (eggs by mitosis offspring
are clones).
Aspidoscelis uniparens is a species that consists
of 3n females that reproduce clonally laying 3n
eggs that divide without fertilization. It
evolved from the diploid species, A. inornata
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• VI. Mutation
• Overview
• Changes in Ploidy
• - These are the most dramatic changes, adding a
  whole SET of chromosomes
• Mechanism 1 Complete failure of Meiosis
• Mechanism 2 Failure of Mitosis in
  Gamete-producing Tissue

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2n
1) Consider a bud cell in the flower bud of a
plant.
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2n
4n
1) Consider a bud cell in the flower bud of a
plant.
2) It replicates its DNA but fails to divide...
Now it is a tetraploid bud cell.
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2n
4n
1) Consider a bud cell in the flower bud of a
plant.
2) It replicates its DNA but fails to divide...
Now it is a tetraploid bud cell.
3) A tetraploid flower develops from this
tetraploid cell eventually producing 2n SPERM
and 2n EGG
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How do we define species? A group of
organisms that reproduce with one another and are
reproductively isolated from other such
groups (E. Mayr biological species concept)
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How do we define species? Here, the
tetraploid population is even reproductively
isolated from its own parent speciesSo
speciation can be an instantaneous genetic
event
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• VI. Mutation
• Overview
• Changes in Ploidy
• - These are the most dramatic changes, adding a
  whole SET of chromosomes
• Mechanism 1 Complete failure of Meiosis
• Mechanism 2 Complete failure of Mitosis
• Mechanism 3 Allopolyploidy - hybridization

Polyploidy occurs here creating a cell with
homologous sets
Black Mustard
gametes
2n 16
n 8
2n 34
n 17
2n 18
n 9
Fertilization produces a cell with non-homologous
chromosomes
New Species
Cabbage
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X
Spartina alterniflora from NA colonized Europe
Spartina maritima native to Europe
Sterile hybrid Spartina x townsendii
Allopolyploidy 1890s
Spartina anglica an allopolyploid and a
worldwide invasive outcompeting native species
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• VI. Mutation
• Overview
• Changes in Ploidy
• - These are the most dramatic changes, adding a
  whole SET of chromosomes
• Mechanism 1 Complete failure of Meiosis
• Mechanism 2 Complete failure of Mitosis
• Mechanism 3 Allopolyploidy - hybridization
• The Frequency of Polyploidy
• For reasons we just saw, we might expect
  polyploidy to occur more frequently in
  hermaphroditic species, because the chances of
  jumping the triploidy barrier to reproductive
  tetraploidy are more likely. Over 50 of all
  flowering plants are polyploid species many
  having arisen by this duplication of chromosome
  number within a lineage.

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• VI. Mutation
• Overview
• Changes in Ploidy
• Changes in aneuploidy (changes in chromosome
  number)
• 1. Mechanism Non-disjunction (failure of a
  homologous pair or
• sister chromatids to separate)

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• VI. Mutation
• Overview
• Changes in Ploidy
• Changes in aneuploidy (changes in chromosome
  number)
• 1. Mechanism Non-disjunction (failure of a
  homologous pair or
• sister chromatids to separate)
• 2. Human Examples
• a. trisomies
• Trisomy 21 Downs Syndrome

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• VI. Mutation
• Overview
• Changes in Ploidy
• Changes in aneuploidy (changes in chromosome
  number)
• 1. Mechanism Non-disjunction (failure of a
  homologous pair or
• sister chromatids to separate)
• 2. Human Examples
• a. trisomies
• Trisomy 21 Downs Syndrome
• Trisomy 18 Edwards Syndrome
• Trisomy 13 Patau Syndrome
• Trisomy 9
• Trisomy 8
• Trisomy 22

Some survive to birth
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• VI. Mutation
• Overview
• Changes in Ploidy
• Changes in aneuploidy (changes in chromosome
  number)
• 1. Mechanism Non-disjunction (failure of a
  homologous pair or
• sister chromatids to separate)
• 2. Human Examples
• a. trisomies
• 47, XXY Klinefelters Syndrome

Extreme effects listed below most show a
phenotype within the typical range for XY males
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• VI. Mutation
• Overview
• Changes in Ploidy
• Changes in aneuploidy (changes in chromosome
  number)
• 1. Mechanism Non-disjunction (failure of a
  homologous pair or
• sister chromatids to separate)
• 2. Human Examples
• a. trisomies
• 47, XXX Triple-X Syndrome

No dramatic effects on the phenotype may be
taller. In XX females, one X shuts down anyway,
in each cell (Barr body). In triple-X females, 2
Xs shut down.
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• VI. Mutation
• Overview
• Changes in Ploidy
• Changes in aneuploidy (changes in chromosome
  number)
• 1. Mechanism Non-disjunction (failure of a
  homologous pair or
• sister chromatids to separate)
• 2. Human Examples
• a. trisomies
• 47, XYY Super-Y Syndrome

Often taller, with scarring acne, but within the
phenotypic range for XY males
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• VI. Mutation
• Overview
• Changes in Ploidy
• Changes in aneuploidy (changes in chromosome
  number)
• 1. Mechanism Non-disjunction (failure of a
  homologous pair or
• sister chromatids to separate)
• 2. Human Examples
• b. monosomies
• 45, XO Turners Syndrome (the only human
  monosomy to survive to birth)

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• VI. Mutation
• Overview
• Changes in Ploidy
• Changes in Aneuploidy (changes in chromosome
  number)
• D. Change in Gene Number/Arrangement

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• VI. Mutation
• Overview
• Changes in Ploidy
• Changes in Aneuploidy (changes in chromosome
  number)
• D. Change in Gene Number/Arrangement
• 1. Mechanism 1 Unequal Crossing-Over
• a. process
• If homologs line up askew

A
B
a
b
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• VI. Mutation
• Overview
• Changes in Ploidy
• Changes in Aneuploidy (changes in chromosome
  number)
• D. Change in Gene Number/Arrangement
• 1. Mechanism 1 Unequal Crossing-Over
• a. process
• If homologs line up askew
• And a cross-over occurs

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• VI. Mutation
• Overview
• Changes in Ploidy
• Changes in Aneuploidy (changes in chromosome
  number)
• D. Change in Gene Number/Arrangement
• 1. Mechanism 1 Unequal Crossing-Over
• a. process
• If homologs line up askew
• And a cross-over occurs
• Unequal pieces of DNA will be exchanged the A
  locus has been duplicated on the lower chromosome
  and deleted from the upper chromosome

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• VI. Mutation
• Overview
• Changes in Ploidy
• Changes in Aneuploidy (changes in chromosome
  number)
• D. Change in Gene Number/Arrangement
• 1. Mechanism 1 Unequal Crossing-Over
• a. process
• b. effects
• - can be bad
• deletions are usually bad reveal deleterious
  recessives
• additions can be bad change protein
  concentration

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• VI. Mutation
• Overview
• Changes in Ploidy
• Changes in Aneuploidy (changes in chromosome
  number)
• D. Change in Gene Number/Arrangement
• 1. Mechanism 1 Unequal Crossing-Over
• a. process
• b. effects
• - can be bad
• deletions are usually bad reveal deleterious
  recessives
• additions can be bad change protein
  concentration
• - can be good
• more of a single protein could be advantageous
  
• (r-RNA genes, melanin genes, etc.)

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• VI. Mutation
• Overview
• Changes in Ploidy
• Changes in Aneuploidy (changes in chromosome
  number)
• D. Change in Gene Number/Arrangement
• 1. Mechanism 1 Unequal Crossing-Over
• a. process
• b. effects
• - can be bad
• deletions are usually bad reveal deleterious
  recessives
• additions can be bad change protein
  concentration
• - can be good
• more of a single protein could be advantageous
  
• (r-RNA genes, melanin genes, etc.)
• source of evolutionary novelty (Ohno
  hypothesis - 1970)

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Gene A
Duplicated A
generations
Mutation may even render the protein non-functio
nal
But this organism is not selected against,
relative to others in the population that lack
the duplication, because it still has the
original, functional, gene.
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Mutation may even render the protein non-functio
nal
Mutation other mutations may render the protein
functional in a new way
So, now we have a genome that can do all the old
stuff (with the original gene), but it can now
do something NEW. Selection may favor these
organisms.
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If so, then wed expect many different
neighboring genes to have similar sequences. And
non-functional pseudogenes (duplicates that had
been turned off by mutation). These occur Gene
Families
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And, if we can measure the rate of mutation in
these genes, then we can determine how much time
must have elapsed since the duplication event
Gene family trees
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• VI. Mutation
• Overview
• Changes in Ploidy
• Changes in Aneuploidy (changes in chromosome
  number)
• D. Change in Gene Number/Arrangement
• Mechanism 1 Unequal Crossing-Over
• Mechanism 2 Inversion (changes the order of
  genes on a chromosome)

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• VI. Mutation
• Overview
• Changes in Ploidy
• Changes in Aneuploidy (changes in chromosome
  number)
• D. Change in Gene Number/Arrangement
• Mechanism 1 Unequal Crossing-Over
• Mechanism 2 Inversion (changes the order of
  genes on a chromosome)

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• VI. Mutation
• Overview
• Changes in Ploidy
• Changes in Aneuploidy (changes in chromosome
  number)
• D. Change in Gene Number/Arrangement
• Mechanism 1 Unequal Crossing-Over
• Mechanism 2 Inversion (changes the order of
  genes on a chromosome)

Chromosomes are no longer homologous along entire
length
B-C-D on top d-c-b on bottom
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• VI. Mutation
• Overview
• Changes in Ploidy
• Changes in Aneuploidy (changes in chromosome
  number)
• D. Change in Gene Number/Arrangement
• Mechanism 1 Unequal Crossing-Over
• Mechanism 2 Inversion (changes the order of
  genes on a chromosome)

Chromosomes are no longer homologous along entire
length
And if a cross-over occurs.
ONE loops to get genes across from each other
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• VI. Mutation
• Overview
• Changes in Ploidy
• Changes in Aneuploidy (changes in chromosome
  number)
• D. Change in Gene Number/Arrangement
• Mechanism 1 Unequal Crossing-Over
• Mechanism 2 Inversion (changes the order of
  genes on a chromosome)

The cross-over products are non-functional, with
deletions AND duplications
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• VI. Mutation
• Overview
• Changes in Ploidy
• Changes in Aneuploidy (changes in chromosome
  number)
• D. Change in Gene Number/Arrangement
• Mechanism 1 Unequal Crossing-Over
• Mechanism 2 Inversion (changes the order of
  genes on a chromosome)

The only functional gametes are those that DID
NOT cross over and preserve the parental
combination of alleles
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• VI. Mutation
• Overview
• Changes in Ploidy
• Changes in Aneuploidy (changes in chromosome
  number)
• D. Change in Gene Number/Arrangement
• Mechanism 1 Unequal Crossing-Over
• Mechanism 2 Inversion (changes the order of
  genes on a chromosome)

Net effect stabilizes sets of genes. This
allows selection to work on groups of alleles
those that work well TOGETHER are selected for
and can be inherited as a co-adapted gene
complex
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• VI. Mutation
• Overview
• Changes in Ploidy
• Changes in Aneuploidy (changes in chromosome
  number)
• D. Change in Gene Number/Arrangement
• Mechanism 1 Unequal Crossing-Over
• Mechanism 2 Inversion (changes the order of
  genes on a chromosome)
• Mechanism 3 Translocation (gene or genes move
  to another homologous set)

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Translocation Downs. Transfer of a 21 chromosome
to a 14 chromosome
Can produce normal, carrier, and Downs child.
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• VI. Mutation
• Overview
• Changes in Ploidy
• Changes in Aneuploidy (changes in chromosome
  number)
• D. Change in Gene Number/Arrangement
• E. Change in Gene Structure
• Mechanism 1 Exon Shuffling
• Crossing over WITHIN a gene, in introns, can
  recombine exons within a gene, producing new
  alleles.

Allele a
EXON 1a
EXON 2a
EXON 3a
Allele A
EXON 1A
EXON 2A
EXON 3A
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• VI. Mutation
• Overview
• Changes in Ploidy
• Changes in Aneuploidy (changes in chromosome
  number)
• D. Change in Gene Number/Arrangement
• E. Change in Gene Structure
• Mechanism 1 Exon Shuffling
• Crossing over WITHIN a gene, in introns, can
  recombine exons within a gene, producing new
  alleles.

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• VI. Mutation
• Overview
• Changes in Ploidy
• Changes in Aneuploidy (changes in chromosome
  number)
• D. Change in Gene Number/Arrangement
• E. Change in Gene Structure
• 1. Mechanism 1 Exon Shuffling
• 2. Mechanism 2 Point Mutations
• a. addition/deletion frameshift mutations

Throws off every 3-base codon from mutation point
onward
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• VI. Mutation
• Overview
• Changes in Ploidy
• Changes in Aneuploidy (changes in chromosome
  number)
• D. Change in Gene Number/Arrangement
• E. Change in Gene Structure
• 1. Mechanism 1 Exon Shuffling
• 2. Mechanism 2 Point Mutations
• a. addition/deletion frameshift mutations
• b. substitution

At most, only changes one AA (and may not change
it)
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• VI. Mutation
• Overview
• Changes in Ploidy
• Changes in Aneuploidy (changes in chromosome
  number)
• D. Change in Gene Number/Arrangement
• E. Change in Gene Structure
• F. Summary

Sources of Variation Causes of Evolutionary
Change MUTATION Natural Selection -New
Genes  point mutation  Mutation
(polyploidy can make new exon
shuffling  species) RECOMBINATION - New
Genes crossing over -New Genotypes
crossing over independent assortment
VARIATION